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Biomedical subjects

J Bolinder

Publications and source records attributed to J Bolinder.

At least 91 records · Page 5Linked to original sources

The Stockholm experience with pancreatic transplantation using enteric exocrine diversion.

Between April 1974 and June 1990, 128 pancreatic transplantations were performed. Of these 117 were with pancreatico-enterostomy. In four consecutive series of combined transplantations in uraemic diabetic patients the 1-year graft survival rate have successively improved (27%, 65%, 68% and 73%). In three similar series of single pancreatic transplantations the results also improved but still remained inferior (0%, 33% and 33%). In a series of combined transplantations performed in preuraemic diabetic patients the 1-year actuarial graft survival rate was only 25%. The results with pancreatic transplantation with pancreatico-enterostomy are now satisfactory. However, immunological loss graft function still constitute a major problem in the non- or pre-uraemic recipients. The metabolic control in patients with functioning grafts is normal or near-normal in the majority of patients followed for at least 1 year.

Diabetes Mellitus, Type 1↗

Long-term metabolic control after pancreas transplantation with enteric exocrine diversion.

Long-term metabolic control after pancreatic transplantation with enteric exocrine diversion was evaluated in 42 Type I (insulin-dependent) diabetic pancreas recipients with functioning grafts for 1 to 7 years. Glycaemic control (fasting blood glucose, glycosylated haemoglobin A1c, oral and intravenous glucose tolerance tests) was normal or near-normal in most patients, and showed no deterioration with time. In ten patients with functioning grafts for 5 years there was a small, but significant, improvement in the glucose control at 3 to 5 years as compared with that at 6 months post-operatively. In the latter recipients the number of acute rejection episodes correlated negatively with the intravenous glucose tolerance at 6 months (r = -0.64, p less than 0.01) and at 5 years (r = -0.60, p less than 0.01) after transplantation, respectively. The glycaemic control at 6 and 12 months after transplantation was similar whether segmental (n = 35) or whole-organ (n = 7) pancreatic grafts had been used. In six non-uraemic recipients who had received a pancreas transplant alone the serum cholesterol increased in all but one patient (0.05 less than p less than 0.1), and the LDL/HDL-cholesterol ratio was significantly higher (p less than 0.005) one year after transplantation than before. Conversely, in six diabetic patients who had lost the function of their single pancreatic grafts the lipid and lipoprotein profiles remained unaltered. It is concluded that the long-term glycaemic control after segmental or whole-organ pancreatic transplantation with enteric exocrine diversion remains essentially normal in most recipients, and it may even improve with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Skin microvascular reactivity in fingers of diabetic patients after combined kidney and pancreas transplantation.

Nine patients with severe late diabetic complications were investigated 2 and 38 months after successful combined kidney and pancreas transplantation. Nine healthy subjects served as controls. Blood cell velocity in single capillaries was evaluated by videophotometric capillaroscopy, and total skin microcirculation of the same area by laser Doppler fluxmetry. The measurements were performed during rest, and post-occlusive (1 min) reactive hyperaemia. Laser Doppler flux was also recorded during venous occlusion. The basal capillary blood cell velocity and laser Doppler flux values increased significantly (p less than 0.05) during the observation period. The time to maximal capillary blood cell velocity during hyperaemia was prolonged 2 months after combined kidney and pancreas transplantation (p less than 0.05), and still more so at 38 months (p less than 0.05). The ability to decrease blood flow during venous occlusion was impaired at 2 months, and was not significantly better at reinvestigation. The results indicate a succesive increase of basal blood flow in the skin microcirculation after successful combined kidney and pancreas transplantation, but no improvement of the impaired microvascular reactivity.

Adult↗

Glucose determination in samples taken by microdialysis by peroxidase-catalyzed luminol chemiluminescence.

An automatic, luminometric assay of glucose in samples of the extracellular water space obtained by microdialysis is described. The assay involves oxidation by glucose oxidase (EC 1.1.3.4) and mutarotation of glucose by aldose mutarotase (EC 5.1.3.3.). The H2O2 formed is subsequently determined in a reaction catalyzed by horseradish peroxidase (EC 1.11.1.7) using luminol as electron donor. The assay is linear between 0.01 and 1 nmol in the cuvette. The detection limit, defined as 3 standard deviations of the reagent blank, was 0.008 mumol/liter in the cuvette. A complete oxidation of glucose is obtained within 4 min and 25 samples are automatically assayed within 75 min. Addition of microdialysate sample obtained from human adipose tissue in vivo did not interfere with the standard curves. Glucose added to microdialysate resulted in a complete recovery compared to a H2O2 standard. Analytical interference from different factors was investigated. No interference was observed up to the following concentrations: 5 mumol/liter epinephrine, 1 mumol/liter norepinephrine, 100 mumol/liter insulin, 500 mumol/liter pyruvate, 50 mmol/liter lactate, and 1 mumol/liter ascorbate. The glucose values with the present method correlated strongly (r = 0.984) with values obtained using a routine method involving glucose oxidase and peroxidase.

Adipose Tissue↗

Adrenergic regulation of lipolysis in human fat cells during exercise.

The adrenergic regulation of lipolysis was studied, before and after 30 min of submaximal exercise, in isolated adipocytes removed from the abdominal and gluteal regions of healthy non-obese men and women. Noradrenaline-induced lipolysis was significantly enhanced in gluteal adipocytes from men but not in women after exercise. However, the pure beta-adrenergic responsiveness was equally increased in gluteal adipocytes of both sexes after exercise, as judged by the effect of isoprenaline. Furthermore, the alpha 2-adrenergic anti-lipolytic responsiveness was more apparent after exercise in females than in males thereby counter-balancing the increase in the beta-adrenergic effect in the gluteal region in the former. The increased beta-adrenergic responsiveness induced by exercise in gluteal adipocytes of males could be mimicked by agents acting at the levels of adenylate cyclase, coupling proteins, phosphodiesterase, and protein kinase and seems to be due to an adaptive enhancement at the hormone-sensitive-lipase level. There was no change in the stoichiometric properties of beta-adrenoceptors of gluteal adipocytes after exercise. Abdominal adipocytes of both sexes were four to five times more responsive to noradrenaline than gluteal ones. However, exercise induced no further enhancement of the catecholamine-stimulated lipolysis rate in fat cells from this site. Thus, the influence of exercise on catecholamine-stimulated lipolysis is regional and sex dependent. Men, but not women, have a greater ability to adapt lipolysis to increasing energy demands during exercise that are due to an acute increase in the effectiveness of the hormone-sensitive lipase complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Pancreatic autoantibodies and pancreatic function in Sjögren's syndrome.

Pancreatic autoantibodies were determined in 49 patients with Sjögren's syndrome and related to functional parameters. Pancreatic duct autoantibodies (PDA) were detected in the sera of three patients, and all showed abnormal exocrine pancreatic function. Islet cell antibodies (ICA) were not detected in the sera of the 49 patients, including two individuals with diabetes mellitus. In conclusion, PDA occur in patients with Sjögren's syndrome, and may be associated with exocrine pancreatic dysfunction.

Autoantibodies↗

Microdialysis of adipose tissue.

Although microdialysis has been available for almost two decades, it has only recently been applied in investigations of adipose tissue. The microdialysis technique enables continuous sampling of metabolites and other small molecules from the extracellular space of subcutaneous adipose tissue from intact animals or man, and the exposure of this compartment locally to metabolically active agents without causing generalized effects. To date, the method has been used to measure the steady-state interstitial levels of metabolites and to investigate the regulation of lipolysis and carbohydrate metabolism in situ in subcutaneous adipose tissue. Apart from a great potential for experimental research, the microdialysis method offers several new possibilities for clinical investigation. Because microdialysis probes are easy to implant and cause little discomfort, they may be used for continuous monitoring of glucose and glycerol (lipolysis index) in the treatment of diabetes, obesity and other disorders characterized by disturbances in lipid and carbohydrate metabolism.

Adipose Tissue↗

Effect of pancreas transplantation on glucose counterregulation in insulin-dependent diabetic patients prone to severe hypoglycaemia.

Pancreatic transplantation was performed in three patients with insulin-dependent diabetes mellitus in whom recurrent and severe episodes of hypoglycaemia had been found to be due to defective glucose counterregulation. Thus in these patients the spontaneous blood glucose recovery after insulin-induced hypoglycaemia (0.1 U kg-1 h-1 i.v. insulin until blood glucose levels fell below 2.8 mmol l-1) was delayed, and the responses of glucagon, epinephrine and growth hormone (GH) were absent or diminished. After pancreas transplantation the patients exhibited essentially normal blood glucose control. When the insulin infusion test was repeated 3 months after the transplantation, the blood glucose level recovered rapidly after insulin withdrawal. The glucagon response was restored, and the responses of epinephrine and GH were improved. Plasma C-peptide was suppressed by approximately 50%, which is less than is observed in normal subjects. It is concluded that glucose counterregulation improves after pancreas transplantation. This appears to be mainly due to an improvement in the hypoglycaemia-induced glucagon response, but an amelioration of sympatho-adrenal and hypothalamic-pituitary regulatory mechanisms may also be involved. The apparent failure to suppress completely the insulin release from the denervated pancreas transplant indicates that inhibition of beta-cell secretion during insulin-induced hypoglycaemia may be partly under neural control.

Adult↗

Effects of insulin deprivation and replacement on in vivo subcutaneous adipose tissue substrate metabolism in humans.

The effects of insulin deprivation and replacement on adipose tissue metabolism were investigated in vivo with microdialysis in nine insulin-dependent diabetic patients with no residual insulin secretion. Dialysis probes, implanted in abdominal subcutaneous fat, were continuously perfused, and tissue dialysate concentrations of glycerol (lipolysis index), glucose, lactate, and pyruvate were determined. Comparisons were made with respective metabolite levels in venous plasma. After termination of intravenous insulin infusion, free insulin in plasma fell from 130 to 70 pM. At the same time, glucose levels in plasma and adipose tissue rose in parallel. However, the relative increase in glucose levels was greater in adipose tissue than in blood. On the other hand, the increase in glycerol concentration in adipose tissue (35%) was markedly less than that in venous plasma (250%). Lactate and pyruvate levels in adipose tissue and blood remained unchanged. After the resumption of intravenous insulin, free insulin in plasma rose to approximately 600 pM. At the same time, the glucose levels in blood and adipose tissue decreased rapidly, and the glycerol concentration in these tissues decreased to 50% of the baseline levels. The lactate and pyruvate levels in subcutaneous tissue increased briefly after insulin replacement, whereas the lactate but not pyruvate levels in blood showed a similar increase. The alpha- or beta-blocking agents phentolamine and propranolol in the ingoing tissue perfusate did not influence tissue glycerol at any time during the experiment. We concluded that insulin-induced changes in circulating metabolites only partly reflect variations in adipose tissue substrate kinetics. During insulin deprivation, glucose is accumulated in the adipose tissue extracellular compartment, probably because of reduced utilization by the adipocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗

Does combined kidney and pancreas transplantation reverse functional diabetic microangiopathy?

Using videophotometric capillaroscopy and laser Doppler fluxmetry, we have investigated skin microvascular reactivity in the fingers of 14 diabetic patients with severe, late complications 20 months after combined kidney and pancreas transplantation. The results were compared with those obtained in 20 diabetic patients awaiting pancreas transplantation and in 19 healthy subjects. The capillary blood cell velocity at rest (P less than 0.01) and during postocclusive reactive hyperemia (P less than 0.05) was significantly lower in both patient groups than in the healthy controls. However, the time to peak capillary blood cell velocity during hyperemia was normal in the post-transplantation group (NS) but significantly prolonged in the pretransplantation group (P less than 0.01). The ability to decrease flow during venous stasis-the so called venoarte-riolar reflex--was strongly impaired in the pretransplantation group (P less than 0.001) but less so in the post-transplantation group (P less than 0.05) as compared to healthy controls. It may be concluded that diabetic patients, after combined kidney and pancreas transplantation, show a tendency towards better microvascular reactivity than those awaiting transplantation.

Adult↗

In vivo subcutaneous adipose tissue glucose kinetics after glucose ingestion in obesity and fasting.

The kinetic pattern of subcutaneous adipose tissue extracellular glucose following glucose ingestion was investigated in vivo with a microdialysis technique in normal-weight (n = 21) and obese subjects (n = 18) before and after a 7-day fast (n = 9). A dialysis probe (4 x 0.5 mm) was implanted subcutaneously, and was continuously perfused (5 microliters/min). The tissue dialysate glucose concentration was determined in 15-min samples before and during a period of 180 min after a 75-g oral glucose load. A comparison was made between the tissue dialysate concentrations and the venous blood glucose levels. In all study groups the increase in subcutaneous tissue dialysate glucose following glucose ingestion paralleled that in blood, with a time-lag of up to 15 min. In the normal-weight subjects the maximum relative increase in abdominal adipose tissue dialysate glucose was 25% higher (p less than 0.005) than the corresponding blood glucose level, and the total relative glucose level (area under curve, AUC) in abdominal fat was 20% (p less than 0.01) higher than in blood. In contrast, the kinetics of gluteal subcutaneous tissue dialysate and blood glucose levels were similar. In the obese patients before the fasting period the maximum relative glucose level in abdominal fat was almost twice as high as in blood (p less than 0.005), and the total glucose level (AUC) was 50% higher than the blood glucose AUC (p less than 0.005). After the fast, on the other hand, almost identical relative dynamics of abdominal subcutaneous tissue and blood glucose levels were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

Subcutaneous adipose tissue: a source of lactate production after glucose ingestion in humans.

The in vivo kinetics of lactate and pyruvate in the extracellular space of subcutaneous adipose tissue after glucose ingestion were investigated in healthy volunteers by the use of a microdialysis sampling technique. Comparison was made with the metabolite levels in venous plasma. The absolute subcutaneous tissue concentrations of lactate and pyruvate were estimated in the fasting state by perfusion with varying lactate- and pyruvate-containing solutions. An equilibrium with the surrounding extracellular fluid was found for both lactate and pyruvate in concentrations similar to those in venous plasma. After glucose ingestion there was an increase in the circulating levels of glucose, lactate, and pyruvate, which returned to base-line values within 3 h. There was a more marked increase in lactate in subcutaneous adipose tissue than in venous blood, and the adipose tissue lactate remained elevated for at least 3 h. In contrast, pyruvate levels increased much less in subcutaneous fat than in venous blood. The addition of isoproterenol (which inhibits adipose tissue glucose metabolism) to the tissue perfusate lowered the subcutaneous tissue lactate levels significantly but did not affect the subcutaneous pyruvate levels. These data suggest that human subcutaneous adipose tissue is a source of in vivo lactate production after glucose ingestion. Since lactate is thought to be a major substrate for glycogen synthesis in the liver, the present findings may provide evidence of a new and important role of the adipose tissue metabolism in the regulation of whole body glucose homeostasis in humans.

Adipose Tissue↗

Adrenergic regulation of lipolysis in situ at rest and during exercise.

The adrenergic regulation of lipolysis was investigated in situ at rest and during standardized bicycle exercise in nonobese healthy subjects, using microdialysis of the extracellular space in subcutaneous adipose tissue. The glycerol concentration was about two times greater in adipose tissue than in venous blood. At rest, the glycerol concentration in adipose tissue was rapidly increased by 100% (P less than 0.01) after the addition of phentolamine to the ingoing perfusate, whereas addition of propranolol did not alter the adipose tissue glycerol level. Glycerol in adipose tissue and plasma increased during exercise and decreased in the postexercise period. Propranolol in the perfusate almost completely inhibited the increase in the tissue dialysate glycerol during the exercise-postexercise period. Phentolamine, however, was completely ineffective in this respect. During exercise, the lipolytic activity was significantly more marked in abdominal than in gluteal adipose tissue; this was much more apparent in women than in men. Thus, in vivo lipolysis in subcutaneous adipose tissue is regulated by different adrenergic mechanisms at rest and during exercise. Alpha-adrenergic inhibitory effects modulate lipolysis at rest, whereas beta-adrenergic stimulatory effects modulate lipolysis during exercise. In addition, regional differences in lipolysis are present in vivo during exercise, which seem governed by factors relating to sex.

Adipose Tissue↗

Pancreatic transplantation using enteric exocrine diversion: the Stockholm experience with 117 cases.

One-hundred twenty-eight pancreatic transplantations were performed between 1974 and 1990; 117 of which were with pancreatico-enterostomy. Combined renal and pancreatic transplantations were performed in 68 uremic patients and in 8 preuremic recipients. Single pancreatic transplantations were performed in 31 recipients and in 6 instances, the pancreatic transplantation was performed in a patient who already had a renal graft. In 4 consecutive series (n = 15, 20, 21, 11) of combined transplantations in uremic diabetic patients, the 1-year graft survival rate has excessively improved markedly (27%, 65%, 68%, and 73%). In 3 similar series of single pancreatic transplantations (n = 7, 13, 6) the results also improved, but still remained inferior (0%, 33%, and 33%). In 42 patients followed for more than 1 year after transplantation, the mean blood glucose tolerance test 4.2 +/- 0.5, HbA1c 5.1 +/- 0.8, 2-hour blood glucose level of the oral glucose tolerance test 6.9 +/- 2.1 and the K-value of the intravenous glucose tolerance test 1.2 +/- 0.6%. The results with pancreatic transplantation with pancreatico-enterostomy are now satisfactory. However, immunological graft losses still constitute a major problem in the non- or preuremic recipients.

Diabetes Mellitus, Type 1↗